Association between non-vascularised bone graft failure and compartment of the defect in mandibular reconstruction: a systematic review and meta-analysis.

Controversy exists regarding the influence of the graft placement site in the mandible on the success of non-vascularised bone grafts. In this study, we examine the association between the compartment of the mandibular defect and the bone graft failure rate. A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Failure rates according to the compartment of mandibular defect were extracted and analysed by meta-analysis. The Newcastle-Ottawa Scale was used to assess the quality of the studies, and publication bias was evaluated using funnel plots. The search strategy identified 27 publications. After screening, five were selected for review. Based on the result of comparison among these five, we found no significant statistical association between the bone graft failure rate and compartment of mandibular defect, although further investigation of prospective randomised cohort studies is required.

Non-tuberculous Mycobacterium infection after transfer of autologous fat to the face: a rare case.

Autologous fat has long been used as a filler in the face, and has recently gained popularity in plastic surgery with a wound infection rate of 1% - 5%. The incidence of mycobacterial infections has increased over recent decades, which is attributed in part to the increased popularity of these procedures.2 Infections by non-tuberculosis mycobacteria often cause chronic inflammation and progressive infection that may eventually manifest themselves as severe scars, fistulas, and hollows, and irregular facial contours. However, few cases of mycobacterial infection have been reported to have been caused by plastic surgery. We present a rare case of non-tuberculosis mycobacterial infection after transfer of autologous fat to the face.

Changes in the expression of α-tocopherol-related genes in liver and mammary gland biopsy specimens of peripartum dairy cows.

Blood α-tocopherol (α-Toc) concentrations decline gradually throughout the prepartum period, reaching the nadir after calving in dairy cows. The 6 α-Toc-related molecules [α-Toc transfer protein (TTPA); afamin; scavenger receptor class B, Type I; ATP-binding cassette transporter A1; tocopherol-associated protein (SEC14L2); and cytochrome P450 family 4, subfamily F, polypeptide 2 (CYP4F2)] are expressed in liver and other peripheral tissues. These molecules could regulate α-Toc transport, blood concentrations, and metabolism of α-Toc. Therefore, the aim of this study was to evaluate the changes in the expression of α-Toc-related genes in liver and mammary gland tissues of dairy cows around calving, which have remained elusive until now. In experiment (Exp.) 1, 28 multiparous Holstein cows were used (from -5 to 6 wk relative to parturition) to monitor the changes in dietary α-Toc intake, blood concentrations of α-Toc, and lipoproteins; in Exp. 2, 7 peripartum Holstein cows were used (from -4 to 4 wk relative to parturition) for liver tissue biopsy; and in Exp. 3, 10 peripartum Holstein cows were used (from -8 to 6 wk relative to parturition) to carry out the mammary gland tissue biopsy and milk sampling. In Exp. 1, the serum α-Toc concentrations declined gradually with decreasing amount of α-Toc intake and plasma high-density lipoprotein concentrations toward calving time. However, in the early lactation period after calving, serum α-Toc concentrations remained at a lower concentration despite the recovery of α-Toc intake and plasma high-density lipoprotein concentrations. In Exp. 2, just after calving, the TTPA, SEC14L2, afamin, and albumin mRNA expression levels in the liver were temporarily downregulated, and the hepatic mRNA levels of endoplasmic reticulum stress-induced unfolded protein response markers and acute-phase response marker increased at calving. In Exp. 3, the concentrations of α-Toc in colostrum were greater than those in precolostrum (samples were collected at wk -1 relative to parturition) and mature milk. The expression of TTPA, SEC14L2, and CYP4F2 mRNA in bovine mammary gland tissue was detected. However, TTPA and SEC14L2 mRNA expressions showed the opposite trends: the expression levels of TTPA mRNA peaked whereas SEC14L2 mRNA reached a nadir at calving. These results indicate that the expression of α-Toc-related genes involved in specific α-Toc transfer and metabolism in the liver and mammary gland are altered during calving. Moreover, these changes might be associated with the maintenance of lower serum α-Toc concentrations after calving.

Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds.

The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (Ne ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and Ne in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15-0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small Ne values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and Ne for each breed reflect the breeding strategy applied. The Ne for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract.

Postweaning changes in the expression of chemerin and its receptors in calves are associated with the modification of glucose metabolism.

Chemerin, originally known as a chemoattractant derived from adipose tissue and the liver, has been reported to have regulatory functions in gluconeogenesis, peripheral insulin sensitivity, and insulin secretion. This study was conducted to assess the postweaning changes in expression of this cytokine and its physiological role in the modification of glucose metabolism associated with weaning. Eighteen tissue samples were collected from Holstein calves (90 d of age; n = 4) to investigate the tissue distributions of chemerin and its receptors genes. was highly expressed in the liver, and secreted chemerin protein was found in the plasma. Among the receptors of chemerin, and were ubiquitously expressed whereas was predominantly expressed in the liver. The changes in glucose metabolism and expression of these genes after weaning were assessed by comparing suckling calves (n = 6) and weaned calves (n = 8) of Japanese Black cattle. No significant difference was observed in plasma glucose levels between suckling and weaned calves (P = 0.22), whereas the plasma level of total ketone bodies was significantly higher in weaned calves (P < 0.01). Plasma levels of insulin and cortisol did not differ between suckling and weaned calves. The mRNA levels of certain key enzymes involved in hepatic gluconeogenesis were also altered; for instance, level was lower in postweaning calves (P < 0.05) and () level tended to be higher after weaning (P = 0.08). However, was not altered after weaning. The plasma levels of hepatic stress indicators were also changed, with aspartate transaminase, alanine transaminase, and lactate dehydrogenase being significantly elevated in postweaning calves (P < 0.05). Chemerin protein in liver tissue was less abundant in weaned calves (P < 0.05), although there were no changes in its transcript levels. The abundance of plasma chemerin protein did not change after weaning (P = 0.95). In summary, these data indicate that as a consequence of weaning, which causes physiological stress and alters hepatic metabolism, chemerin protein expression within the liver is downregulated, indicating that chemerin plays a role in the upregulation of hepatic expression via its inhibitory effect on hepatic gluconeogenesis.

Malva verticillata seed extracts upregulate the Wnt pathway in human dermal papilla cells.

OBJECTIVE: Mesenchymal-epithelial interactions are important in controlling hair growth and the hair cycle. The ß-catenin pathway of dermal papilla cells (DPCs) plays a pivotal role in morphogenesis and normal regeneration of hair follicles. Deletion of ß-catenin in the dermal papilla reduces proliferation of the hair follicle progenitor cells that generate the hair shaft and induces an early onset of the catagen phase. In this study, a modulator of the Wnt/ß-catenin activity was studied in oriental herb extracts on cultured human DPCs. METHODS: The effect of Malva verticillata (M. verticillata) seeds on human DPCs was investigated by a Wnt/ß-catenin reporter activity assay system (ß-catenin-TCF/LEF reporter gene) and cell proliferation analysis. The synthesis of the factors related to hair growth and cycling was measured at both the mRNA and the protein level by semi-quantitative PCR and Western blot analysis, respectively. RESULTS: An extract from M. verticillata seeds increased Wnt reporter activity in a concentration-dependent manner and also led to increased ß-catenin levels in cultured human DPCs. Myristoleic acid, identified as an effective compound of M. verticillata seeds, stimulated the proliferation of DPCs in a dose-dependent manner and increased transcription levels of the downstream targets: IGF-1, KGF, VEGF and HGF. Myristoleic acid also enhanced the phosphorylation of MAPKs (Akt and p38). CONCLUSION: Overall, the data suggest that this extract of M. verticillata seeds could be a good candidate for treating hair loss by modulating the Wnt/ß-catenin pathway in DPCs.

Expression of α-tocopherol-associated genes and α-tocopherol accumulation in Japanese Black (Wagyu) calves with and without α-tocopherol supplementation.

The aim of the study was to clarify 1) the distribution of 6 α-tocopherol (α-Toc)-associated gene expressions in 20 major tissues, including metabolic, reproductive, endocrine, immune, and digestive and absorptive tissues, in relation to α-Toc status and 2) the change in expression patterns of the genes induced when α-Toc was orally administered to Japanese Black (JB) calves. This study examined weaned male JB calves ( = 10), of which 5 calves were orally administered α-Toc for 2 wk (30 IU·kg BW·d; TOC group). The others did not receive the α-Toc supplement and were the control (CONT) group. The 20 tissues and venous blood (serum) were sampled on the final day. In both groups, the mean mRNA expression levels for α-Toc transfer protein, afamin (AFM), ATP-binding cassette transporter A1, and tocopherol-associated protein were greatest in the liver ( < 0.05), whereas scavenger receptor class B, Type I (SR-BI) mRNA was greatest in the adrenal gland ( < 0.05). The gene for cytochrome P450 family 4, subfamily F, polypeptide 2 was most highly expressed in the liver, testes, and adrenal gland. The α-Toc content was greatest ( < 0.05) in the testes of the 20 sampled tissues in the CONT group. However, the levels in the testes and jejunum were similar and greater ( < 0.05) than the levels in the other 18 tissues in the TOC group. The mean increase in α-Toc levels after oral α-Toc administration (mean α-Toc content for the TOC group divided by the CONT group content) were greater ( < 0.05) in the jejunum (40.7-fold) and duodenum and liver (26.3- and 23.1-fold) than in the serum (7.8-fold). In the liver, α-Toc administration significantly increased ( < 0.05) the AFM and SR-BI mRNA expression levels. The results show that the liver may play an important role in the regulation of α-Toc disposition, but other peripheral tissues that accumulate large amounts of α-Toc could moderate the local α-Toc status and functions, as inferred from the high expressions of the α-Toc-associated genes in JB calves.

Genetic parameters for yearling weight, carcass traits, and primal-cut yields of Hanwoo cattle.

Genetic parameters associated with yearling weight, carcass traits, and primal-cut yields of male Hanwoo cattle were investigated using univariate and bivariate animal models. The mean yearling weight (YWT), carcass weight (CWT), longissimus muscle area (LMA), backfat thickness (BFT), and marbling score (MS) were 352.47 ± 0.40 kg, 337.39 ± 0.64 kg, 78.28 ± 0.13 cm2, 8.45 ± 0.05 mm, and 3.25 ± 0.03, respectively. Total primal-cut yield (TPC) was 78.95 ± 0.10% of CWT, of which 42.3% was contributed by the forequarters (chuck, CHK; shoulder, SLD; ribs, RIB; and brisket and flank, BAF). Loins, top round (TRND), and round (RND) were associated with yields of 13.57%, 5.45 ± 0.01%, and 8.87 ± 0.02%, respectively. The largest cut studied was ribs (15.67 ± 0.03%). The estimated heritabilities (h2) of YWT, CWT, LMA, BFT, and MS were 0.18 ± 0.02, 0.29 ± 0.04, 0.38 ± 0.05, 0.45 ± 0.05, and 0.62 ± 0.07, respectively. Shoulder yield was highly heritable in Hanwoo steers (0.83 ± 0.13), followed by the yields of round (0.66 ± 0.12), striploin (0.64 ± 0.12), top round (0.62 ± 0.12), sirloin (0.60 ± 0.12), and total primal-cut yield (0.52 ± 0.11). The h2 values of CHK, BAF, RIB, and tenderloin (TLN) ranged from 0.19 ± 0.09 to 0.41 ± 0.11. Generally, the genetic CV was low for most traits (2.33%-6.15%), except for CHK, BFT, and MS. The genetic correlation (rg) was strong between YWT and CWT (0.77 ± 0.06). The greatest positive and negative rg among carcass traits were those between LMA and CWT (0.52 ± 0.08) and between LMA and BFT (-0.30 ± 0.09), respectively. The correlation between CHK and SLD (0.81 ± 0.14), and those between SLD, TLN, TRND, and RND, were mostly strong (0.77-0.87), but the rg between RIB and other traits were strongly negative. The TPC yield showed moderate to high rg with most primal cuts. The YWT, CWT, and LMA correlated notably with CHK, SLD, and loin yields, especially LMA. However, BFT and MS were negatively correlated with many primal cuts but RIB. Those rg estimates were also opposite of that of LMA and CWT with primal cuts. Phenotypic correlations (rp) were generally weaker than rg estimates. The rp of YWT, CWT, and LMA were either zero or moderately negative compared to those of the BFT and MS with primal cuts. Most primal cuts yielded positive rp estimates among them, except for RIB. Our results suggest that direct selection for YWT, various carcass traits, and primal-cut yields may increase the carcass value of Hanwoo males.

Proteomic Analysis Reveals PGAM1 Altering cis-9, trans-11 Conjugated Linoleic Acid Synthesis in Bovine Mammary Gland.

cis-9, trans-11 Conjugated linoleic acid (CLA) is one of the most extensively studied CLA isomers due to its multiple isomer-specific effects. However, the molecular mechanisms of cis-9,trans-11 CLA synthesis in ruminant mammary gland are still not clearly understood. This process may be mediated, to a certain extent, by trans-11 C18:1 regulated by stearoyl-CoA desaturase-1 (SCD1) and/or its syntrophic proteins. This study aimed to investigate the effects of TVA on SCD1-mediated cis-9,trans-11 CLA synthesis in MAC-T cells and its potential molecular mechanism. Results showed that trans-11 C18:1 was continually taken up and converted into cis-9,trans-11 CLA in MAC-T cells during the 4-h incubation of 50 µM trans-11 C18:1. SCD1 protein expression increased more than twofold at 2 h (P < 0.01) and 2.5 h (P < 0.05) before decreasing to less than half of the normal level at 4 h (P < 0.05). One up-regulated (RAS guanyl releasing protein 4 isoform 1 [RASGRP4]) and six down-regulated proteins (glucosamine-6-phosphate deaminase 1 [GNPDA1], triosephosphate isomerase [TPI1], phosphoglycerate mutase 1 [PGAM1], heat shock protein beta-1 [HSPB1], annexin A3 [ANXA3], thiopurine S-methyltransferase [TPMT]) were found in MAC-T cells treated with trans-11 C18:1. Of these seven identified proteins, the presence of GNPDA1 and PGAM1 was verified in several models. More trans-11 C18:1 was taken up after PGAM1 knockdown by small interfering RNA (siRNA). In conclusion, our data suggested that PGAM1 may have a negative relationship with SCD1 and seemed to be involved in cis-9, trans-11 CLA synthesis by facilitating the absorption of trans-11 C18:1 in the bovine mammary gland.

The regulation of oxytocin receptor gene expression during adipogenesis.

Although it has been reported that oxytocin stimulates lipolysis in adipocytes, changes in the expression of oxytocin receptor (OTR) mRNA in adipogenesis are still unknown. The present study aimed to investigate the expression of OTR mRNA during adipocyte differentiation and fat accumulation in adipocytes. OTR mRNA was highly expressed in adipocytes prepared from mouse adipose tissues compared to stromal-vascular cells. OTR mRNA expression was increased during the adipocyte differentiation of 3T3-L1 cells. OTR expression levels were higher in subcutaneous and epididymal adipose tissues of 14-week-old male mice compared to 7-week-old male mice. Levels of OTR mRNA expression were higher in adipose tissues at four different sites of mice fed a high-fat diet than in those of mice fed a normal diet. The OTR expression level was also increased by refeeding for 4 h after fasting for 16 h. Oxytocin significantly induced lipolysis in 3T3-L1 adipocytes. In conclusion, a new regulatory mechanism is demonstrated for oxytocin to control the differentiation and fat accumulation in adipocytes via activation of OTR as a part of the hypothalamic-pituitary-adipose axis.

The anteroposterior axis of the tibia in Korean patients undergoing total knee replacement.

The aim of this study was to find anatomical landmarks for rotational alignment of the tibial component in total knee replacement (TKR) in a CT-based study. Pre-operative CT scanning was performed on 94 South Korean patients (nine men, 85 women, 188 knees) with osteoarthritis of the knee joint prior to TKR. The tibial anteroposterior (AP) axis was defined as a line perpendicular to the femoral surgical transepicondylar axis and passing through the centre of the posterior cruciate ligament (PCL). The angles between the defined tibial AP axis and anatomical landmarks at various levels of the tibia were measured. The mean values of the angles between the defined tibial AP axis and the line connecting the anterior border of the proximal third of the tibia to the centre of the PCL was -0.2° (-17 to 14.1, sd 4.1). This was very close to the defined tibial axis, and remained so regardless of lower limb alignment and the degree of tibial bowing. Therefore, AP axis defined as described, is a reliable anatomical landmark for rotational alignment of tibial components.

Reduced IRE1α mediates apoptotic cell death by disrupting calcium homeostasis via the InsP3 receptor.

The endoplasmic reticulum (ER) is not only a home for folding and posttranslational modifications of secretory proteins but also a reservoir for intracellular Ca(2+). Perturbation of ER homeostasis contributes to the pathogenesis of various neurodegenerative diseases, such as Alzheimer's and Parkinson diseases. One key regulator that underlies cell survival and Ca(2+) homeostasis during ER stress responses is inositol-requiring enzyme 1α (IRE1α). Despite extensive studies on this ER membrane-associated protein, little is known about the molecular mechanisms by which excessive ER stress triggers cell death and Ca(2+) dysregulation via the IRE1α-dependent signaling pathway. In this study, we show that inactivation of IRE1α by RNA interference increases cytosolic Ca(2+) concentration in SH-SY5Y cells, leading to cell death. This dysregulation is caused by an accelerated ER-to-cytosolic efflux of Ca(2+) through the InsP3 receptor (InsP3R). The Ca(2+) efflux in IRE1α-deficient cells correlates with dissociation of the Ca(2+)-binding InsP3R inhibitor CIB1 and increased complex formation of CIB1 with the pro-apoptotic kinase ASK1, which otherwise remains inactivated in the IRE1α-TRAF2-ASK1 complex. The increased cytosolic concentration of Ca(2+) induces mitochondrial production of reactive oxygen species (ROS), in particular superoxide, resulting in severe mitochondrial abnormalities, such as fragmentation and depolarization of membrane potential. These Ca(2+) dysregulation-induced mitochondrial abnormalities and cell death in IRE1α-deficient cells can be blocked by depleting ROS or inhibiting Ca(2+) influx into the mitochondria. These results demonstrate the importance of IRE1α in Ca(2+) homeostasis and cell survival during ER stress and reveal a previously unknown Ca(2+)-mediated cell death signaling between the IRE1α-InsP3R pathway in the ER and the redox-dependent apoptotic pathway in the mitochondrion.

Increased plasma ghrelin suppresses insulin release in wethers fed with a high-protein diet.

Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein (HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet.

Temporal variation of volatile organic compounds and their major emission sources in Seoul, Korea.

This study examines the characteristics of volatile organic compounds (VOCs) and their major emission sources at the Bulgwang site in Seoul, Korea. The annual levels of VOCs (96.2-121.1 ppb C) have shown a decreasing trend from 2004 to 2008. The most abundant component in Seoul was toluene, which accounted for over 23.5 % of the total VOCs on the parts per billion on a carbon basis, and the portions of alkanes with two to six carbons constituted the largest major lumped group, ranging from 40.1 to 48.4 % (45.3 ± 3.7 %) of the total VOCs. Major components of the solvent (toluene, m/p-xylene, o-xylene, and ethylbenzene) showed high in daytime and summer and low in nighttime and winter due mainly to the variation of the ambient temperature. The species mostly emitted from gasoline vapor (i/n-butane, i/n-pentane, n-hexane, and 2-methylpentane) and vehicular exhaust (ethylene, acetylene, and benzene) showed bimodal peaks in the diurnal variation around the commuting hours because of the high traffic volume. For the 14 out of 15 highest concentration species, the weekend effect was only evident on Sundays because of the stepwise implementation of the 5-day work-week system. Principal components analysis (PCA) was applied in order to identify the sources of the 15 highest concentration VOCs and, as a result, three principal components such as gasoline vapor (48.9 %), vehicular exhaust (17.9 %), and evaporation of solvents (9.8 %) were obtained to explain a total of 76.6 % of the data variance. Most influential contributing sources at the sampling site were traffic-related ones although the use of solvent was the dominant emission source based on the official emission inventory.

Genetic polymorphisms and protein structures in growth hormone, growth hormone receptor, ghrelin, insulin-like growth factor 1 and leptin in Mehraban sheep.

The somatotropic axis, the control system for growth hormone (GH) secretion and its endogenous factors involved in the regulation of metabolism and energy partitioning, has promising potentials for producing economically valuable traits in farm animals. Here we investigated single nucleotide polymorphisms (SNPs) of the genes of factors involved in the somatotropic axis for growth hormone (GH1), growth hormone receptor (GHR), ghrelin (GHRL), insulin-like growth factor 1 (IGF-I) and leptin (LEP), using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods in 452 individual Mehraban sheep. A nonradioactive method to allow SSCP detection was used for genomic DNA and PCR amplification of six fragments: exons 4 and 5 of GH1; exon 10 of GH receptor (GHR); exon 1 of ghrelin (GHRL); exon 1 of insulin-like growth factor-I (IGF-I), and exon 3 of leptin (LEP). Polymorphisms were detected in five of the six PCR products. Two electrophoretic patterns were detected for GH1 exon 4. Five conformational patterns were detected for GH1 exon 5 and LEP exon 3, and three for IGF-I exon 1. Only GHR and GHRL were monomorphic. Changes in protein structures due to variable SNPs were also analyzed. The results suggest that Mehraban sheep, a major breed that is important for the animal industry in Middle East countries, has high genetic variability, opening interesting prospects for future selection programs and preservation strategies.

Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer.

BACKGROUND: Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy. METHODS: A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway. RESULTS: For cetuximab regimens, patients homozygous for the wild-type alleles (GG) of LIFR rs3729740 exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (GA and AA; P=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (TT) of ANXA11 rs1049550 exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (CC and CT; P=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type LIFR rs3729740 patients either with wild-type KRAS or skin toxicity (P=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type LIFR rs3729740 (P=0.044) and in those expressing minor-type ANXA11 rs1049550 (P=0.007), respectively. CONCLUSION: LIFR rs3729740 and possibly ANXA11 rs1049550 may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.

Cooperative role of RanBP9 and P73 in mitochondria-mediated apoptosis.

Mitochondrial dysfunction and synaptic damage are critical early features of Alzheimer's disease (AD) associated with amyloid ß (Aß) and τ. We previously reported that the scaffolding protein RanBP9, which is overall increased in AD, simultaneously promotes Aß generation and focal adhesion disruption by accelerating the endocytosis of APP and ß1-integrin, respectively. Moreover, RanBP9 induces neurodegeneration in vitro and in vivo and mediates Aß-induced neurotoxicity. However, little is known regarding the mechanisms underlying such neurotoxic processes. Here, we show that RanBP9 induces the loss of mitochondrial membrane potential and increase in mitochondrial superoxides associated with decrease in Bcl-2, increase in Bax protein and oligomerization, fragmentation of mitochondria, and cytochrome c release. RanBP9-induced neurotoxic changes are significantly prevented by the mitochondrial fission inhibitor Mdivi-1 and by classical inhibitors of the mitochondrial apoptosis, XIAP, Bcl-2, and Bcl-xl. RanBP9 physically interacts with the tumor suppressor p73 and increases endogenous p73α levels at both transcriptional and post-translational levels;moreover, the knockdown of endogenous p73 by siRNA effectively blocks RanBP9 and Aß1-42-induced mitochondria-mediated cell death. Conversely, siRNA knockdown of endogenous RanBP9 also suppresses p73-induced apoptosis, suggesting that RanBP9 and p73 have cooperative roles in inducing cell death. Taken together, these finding implicate the RanBP9/p73 complex in mitochondria-mediated apoptosis in addition to its role in enhancing Aß generation.

Effect of nutrient intake on intramuscular glucose metabolism during the early growth stage in cross-bred steers (Japanese Black male × Holstein female).

The objective was to investigate the impact of nutrient intake during the early growth period on the expression of glucose metabolism-related genes in skeletal muscle of cross-bred cattle. From 1.5 to 5 months of age, group H (n=7) animals were intensively fed a high-protein and low-fat milk replacer [crude protein (CP) 28%; ether extracts (EE) 18%; max: 2.0 kg, 12 l/day], and group R (n=7) animals were fed a restricted amount of normal milk replacer (CP 25%; EE 23%; max 0.5 kg, 4 l/day). From 6 to 10 months of age, group H cattle were fed a high-nutrition total mixed ration mainly prepared from grain feed, and group R cattle were fed only roughage. Blood samples were taken from each animal at three biopsy times (1.5, 5 and 10 months of age), and the blood plasma concentration of glucose and insulin was analysed. In glucose concentration, there were no significant differences; however, the concentrations of insulin were higher in group H than in group R at 5 and 10 months of age. Muscle samples were taken by biopsy from longissimus thoracis muscle (LT) at 1.5, 5 and 10 months of age. We analysed mRNA expression levels using the quantitative real-time polymerase chain reaction (PCR) assay for glucose transporters (GLUT1 and GLUT4), insulin receptor, phosphatidylinositol 3-kinase (PI-3K), protein kinase B (PKB, also known as Akt), hexokinase 1 (HK1) and tumour necrosis factor alpha (TNFα). Although no differences were detected at 1.5 and 5 months of age, at 10 months of age, GLUT1, HK1 and TNFα mRNA expression levels were significantly higher in group H than in group R. These results suggested Glut1 that affects insulin-independently mediated glucose uptake was more responsive to improved nutrition during early growth stage than GLUT4 that insulin-dependently mediated glucose uptake in LT of cattle.